Background: The treatment landscape for relapsed/refractory multiple myeloma (RRMM) has expanded with BCMA- and GPRC5D-directed CAR T-cell therapies and bispecific antibodies (BsAb), which differ in treatment logistics, durability of response, and toxicity profiles, including cytokine release syndrome (CRS), immune effector cell–associated neurotoxicity syndrome (ICANS), infections, and prolonged cytopenias. Comparative real-world data between these modalities remain limited. This study aims to compare treatment-related toxicities between CAR T-cell and bispecific antibody therapies in RRMM, with secondary objectives assessing duration of response, infection risk, hematologic recovery, and timing of CRS and ICANS.
Methods: This single-center, retrospective study included adult patients (≥18 years) with RRMM who received BCMA-directed CAR T-cell therapy with idecabtagene vicleucel or ciltacabtagene autoleucel or BsAb therapy with teclistamab, elranatamab, and talquetamab between March 1, 2021, and February 28, 2025. Descriptive and comparative statistical analyses were conducted to evaluate differences between treatment modalities. The primary objective was to compare treatment-related toxicities, including the incidence and severity of CRS, ICANS, cytopenia, and infections, between patients receiving CAR T-cell therapy and BsAb therapy for relapsed/refractory multiple myeloma. The key secondary objective included duration of response.
Results: A total of 59 adult patients with relapsed or refractory multiple myeloma were included in the study, with 34 receiving CAR T-cell therapy (idecabtagene vicleucel or ciltacabtagene autoleucel) and 25 receiving bispecific antibodies (teclistamab, talquetamab, or elranatamab). Mean age at treatment initiation was similar between CAR T and bispecific therapy groups (62 vs 65 years), as was the median number of prior lines of therapy (4 vs 4). CRS occurred in 66.1% (39/59) patients. Among those with CRS, the maximum documented grade was grade 1 in 69.2% (27/39) patients, followed by grade 2 in 25.6% (10/39), and grade 3 in 5.1% (2/39) patients. CRS occurred more frequently with CAR T therapy compared with bispecific antibodies (73.5% vs 56.0%). ICANS was observed in 18.6% (11/59) patients and occurred at similar rates between those receiving CAR T and bispecific antibody therapy (17.6% vs. 20%). Cytopenias, defined as neutropenia (ANC <1,000 cells/µL) and/or thrombocytopenia (platelets <50 ×10⁹/L), were identified in 39% (23/59) of patients and occurred more frequently with CAR T therapy compared with bispecific antibody therapy (65.2% vs 34.8%). Documented infections occurred in 10/59 (16.9%) patients and were observed at equal rates between CAR T-cell and bispecific antibody therapies. For secondary outcome, the analysis included a total of 35 patients, with 25 patients in the CAR T-cell therapy group and 10 patients in the bispecific antibody group. Patients who received CAR T-cell therapy had longer duration of response. There was a significant difference in duration of response between the two groups (p=0.012).
Conclusions: In this single-center retrospective study, CAR T-cell and bispecific antibody therapies demonstrated comparable overall safety profiles in patients with relapsed or refractory multiple myeloma. Incidence of grade 1 CRS was common and occurred more frequently with CAR T therapy. ICANS and infections occurred at similar rates between treatment groups, while cytopenias were observed more often in patients receiving CAR T therapy. These findings provide real-world insight into the safety profiles of emerging therapies used in the relapsed or refractory setting and may help inform clinical decision-making as use of these agents continues to expand.
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